efficacy and tolerability of beclomethasone dipropionate 100 µg + formoterol 6 µg pmdi via hfa-134a vs. budesonide 160 µg + formoterol 4,5 µg dry powder via turbuhaler®. (symbicort®)

Conditions: Bronchial Asthma

Summary: the aim of this study was to compare the efficacy and tolerability of the fixed combination beclomethasone/formoterol pmdi with that of budesonide/formoterol dry powder via turbuhaler.

asthma is a chronic disease that is estimated to affect over 25 million people both in the u.s. and in europe (i.e. approximately 10% of the total population). pharmacological therapy is used to treat reversible airway obstruction, inflammation and hyper-reactivity. medications include preventive treatments in forms of antinflammatory/antiallergic agents (i.e. glucocorticosteroids, leukotriene antagonists, cromolyn sodium) and reliever treatments, in forms of bronchodilators (i.e. β-adrenergic agonists, anticholinergics). in patients treated with inhaled glucocorticosteroids whose asthma is not fully controlled, national and international guidelines recommend a stepwise approach. recent evidence-based clinical trials show that the addition of a laba to inhaled glucocorticosteroids is more beneficial in terms of asthma control than increasing the dose of corticosteroids alone. comparisons: chf 1535 (beclomethasone dipropionate 100 µg+ formoterol 6 µg) pmdi via hfa-134a compared to symbicort (budesonide 160 µg + formoterol 4,5 µg).

Eligibility criteria:
inclusion criteria: * clinical diagnosis of moderate to severe persistent asthma for at least 6 months, according to gina revised version 2002 guidelines: * forced expiratory volume (fev1) or peak expiratory flow rate (pefr) \> 50% and \< 80% of the predicted normal; * asthma not adequately controlled with the current therapies, defined as presence of daily asthma symptoms \> once a week and night-time asthma symptoms \> twice a month, and daily use of short-acting β2-agonists. these findings are to be based on recent medical history and are to be confirmed in the 2-week run-in period. * treatment with inhaled corticosteroids at a daily dose ≤ 1000 μg of bdp or equivalent. the daily dose of inhaled corticosteroids taken at visit 1 will be assessed taking into account the following ratios between the doses of the different steroids: fluticasone propionate : bdp cfc = 1 : 2; budesonide : bdp cfc = 4 : 5; flunisolide : bdp cfc = 1 : 1. the ratios between inhaled steroids are irrespective of the formulations (i.e. spray aerosol or powder) used. when bdp is given in the new extra-fine hfa-134a formulation (as qvar®, 3m healthcare), the ratio with bdp cfc is set as 2 : 5. therefore, the maximum allowed daily dose of inhaled corticosteroids at study entry will be: budesonide 800 μg, fluticasone propionate 500 μg, flunisolide 1000 μg, bdp 1000 mcg, bdp hfa extra-fine 400 μg. * positive response to the reversibility test in the screening visit, defined as an increase of at least 12% (or, alternatively, of 200ml) from baseline value in the measurement of fev1 30 minutes following 2 puffs (2 x 100 µg) of inhaled salbutamol administered via pmdi. the reversibility test can be avoided in patients having a documented positive response in the previous 6 months. * a co-operative attitude and ability to be trained to correctly use the metered dose inhalers and to complete the diary cards. * written informed consent obtained. * at the end of the 2-week run-in period, the presence of daily asthma symptoms (of at least mild intensity) and nighttime asthma symptom (of at least mild intensity) \> once a week, as well as of daily use of relief salbutamol is to be confirmed by reviewing the diary cards for run-in exclusion criteria: * inability to carry out pulmonary function testing; * diagnosis of chronic obstructive pulmonary disease (copd) as defined by the national heart lung and blood institute/world health organisation (nhlbi/who) global initiative for chronic obstructive lung disease (gold) guidelines (30); * history of near fatal asthma; * evidence of severe asthma exacerbation or symptomatic infection of the airways in the previous 8 weeks; * three or more courses of oral corticosteroids or hospitalisation due to asthma during the previous 6 months; * patients treated with long-acting β2-agonists, anticholinergics and antihistamines during the previous 2 weeks, with topical or intranasal corticosteroids and leukotriene antagonists during the previous 4 weeks; * patients who have changed their dose of inhaled corticosteroids during the previous 4 weeks, or treatment with inhaled corticosteroids at a daily dose \> 1000 μg of bdp or equivalent (except for extra-fine formulations, see inclusion criteria); * current smokers or recent (less than one year) ex-smokers, defined as smoking at least 10 cigarettes/day; * history or current evidence of heart failure, coronary artery disease, myocardial infarction, severe hypertension, cardiac arrhythmias; * diabetes mellitus; * percutaneous transluminal coronary angioplasty (ptca) or coronary artery by-pass graft (cabg) during the previous six months; * patients with an abnormal qtc interval value in the ecg test, defined as \> 450 msec in males or \> 470 msec in females; * other haemodynamic relevant rhythm disturbances (including atrial flutter or atrial fibrillation with ventricular response, bradycardia (≤ 55 bpm), evidence of atrial-ventricular (av) block on ecg of more than 1st degree; * clinically significant or unstable concurrent diseases: uncontrolled hyperthyroidism, significant hepatic impairment, poorly controlled pulmonary (tuberculosis, active mycotic infection of the lung), gastrointestinal (e.g. active peptic ulcer), neurological or haematological autoimmune diseases; * cancer or any chronic diseases with prognosis \< 2 years; * pregnant or lactating females or females at risk of pregnancy, i.e. those not demonstrating adequate contraception (i.e. barrier methods, intrauterine devices, hormonal treatment or sterilization). a pregnancy test is to be carried out in women of a fertile age. * history of alcohol or drug abuse; * patients treated with monoamine oxidase inhibitors, tricyclic antidepressants or beta-blockers as regular use; * allergy, sensitivity or intolerance to study drugs and/or study drug formulation ingredients; * patients unlikely to comply with the protocol or unable to understand the nature, scope and possible consequences of the study; * patients who received any investigational new drug within the last 12 weeks; * patients who have been previously enrolled in this study; * at the end of the run-in period, patients will not be admitted to the treatment period in the case of an increase of pefr (l/sec) measured at the clinics at the end of the run-in period \> 15% in respect of values measured at the start of the run-in period; * patients with asthma exacerbations during the run-in period will also be excluded from the study.

Keywords: asthma combinations inhaled therapy corticosteroids long acting bronchodilators beclomethasone formoterol budesonide